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We present a method, CamShift, for the rapid and accurate prediction of NMR chemical shifts from protein structures. The calculations performed by CamShift are based on an approximate expression of the chemical shifts in terms of polynomial functions of interatomic distances. Since these functions are very fast to compute and readily differentiable, the(More)
NMR spectroscopy plays a major role in the determination of the structures and dynamics of proteins and other biological macromolecules. Chemical shifts are the most readily and accurately measurable NMR parameters, and they reflect with great specificity the conformations of native and nonnative states of proteins. We show, using 11 examples of proteins(More)
Many biochemical processes proceed through the formation of functionally significant intermediates. Although the identification and characterization of such species can provide vital clues about the mechanisms of the reactions involved, it is challenging to obtain information of this type in cases where the intermediates are transient or present only at low(More)
Trunkamide A (1) is a cyclic heptapeptide extracted from the ascidian Lissoclinum sp. and has shown very promising cytotoxic activity. This compound incorporates several of the motifs commonly observed in the Patellin family, including dimethylallyl (Dma) Thr and Ser side chains and a thiazoline heterocycle. Given that little is known about the structures(More)
It has been suggested that the fluctuations of the alignment tensor can affect the results of procedures for characterizing the structure and the dynamics of proteins using residual dipolar couplings. We show here that the very significant fluctuations of the steric alignment tensor caused by the dynamics of proteins can be safely ignored when they do not(More)
Correlated motions in proteins can mediate fundamental biochemical processes such as signal transduction and allostery. The mechanisms that underlie these processes remain largely unknown due mainly to limitations in their direct detection. Here, based on a detailed analysis of protein structures deposited in the protein data bank, as well as on(More)
Oligomerization in the heat shock protein (Hsp) 70 family has been extensively documented both in vitro and in vivo, although the mechanism, the identity of the specific protein regions involved and the physiological relevance of this process are still unclear. We have studied the oligomeric properties of a series of human Hsp70 variants by means of(More)
The applied interaction of synthetic molecules with defined regions of protein surfaces is an emerging strategy for the modulation of protein activity and/or stability. In spite of recent advances, the design of these molecules is not trivial. Among the most challenging aspects in designing these compounds is that they must compete with water molecules for(More)
We review the role conformational ensembles can play in the analysis of biomolecular dynamics, molecular recognition, and allostery. We introduce currently available methods for generating ensembles of biomolecules and illustrate their application with relevant examples from the literature. We show how, for binding, conformational ensembles provide a way of(More)
Proteins with a high propensity to aggregate can be largely prevented from doing so with surprisingly small changes to their primary structure. By using a combination of rational design and quantitative measurements of aggregation rates, we show that adding a single charge in specific "gatekeeper" regions is sufficient to change the timescale for amyloid(More)